Emerging evidence implicates that low levels of ATP in the extracellular space may contribute to the pathophysiology of major depressive disorder (MDD). The concentration of extracellular ATP is regulated by its hydrolase ectonucleotide tri(di)phosphohydrolase (ENTPD). However, the role of ENTPD in depression remains poorly understood. Here we examine the role of CD39 (known as ENTPD1) in mouse depression-like behavior induced by chronic social defeat stress (CSDS). We demonstrate that CSDS enhances the expression and activity of CD39 in hippocampus. The CD39 functional analog apyrase also induces depression-like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD39 has an antidepressant-like effect via increasing hippocampal extracellular ATP concentration, accompanied with an increase in hippocampal neurogenesis and dendritic spine numbers in defeated mice. These results suggest that hippocampal CD39 contributes to CSDS-induced depression-like behavior via hydrolyzing extracellular ATP, indicating that CD39 may be a promising new target for the treatment of depression. © 2020 The Authors.OBJECTIVE The aim of this study is to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. https://www.selleckchem.com/products/gw788388.html A secondary aim is to establish factors associated with (pre-) malignant alterations in a polyp. DESIGN A retrospective cohort study SETTING Maastricht University Medical Centre (MUMC+) and Máxima Medical Centre in Eindhoven/Veldhoven (Máxima MC). POPULATION Women who underwent a hysteroscopic polyp resection between 2008 and 2016. METHODS Patient characteristics and histopathology results of the polyp and, in case of a hysterectomy, the uterus were collected from patients' charts. RESULTS A total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathologic assessment showed no additional (pre-)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors in consideration were significantly associated with (pre-)malignant changes in a polyp. CONCLUSION The incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo-oophorectomy. No prognostic factor for (pre-)malignant changes in a polyp were established. This article is protected by copyright. All rights reserved.BACKGROUND The NSW Clinical Excellence commission introduced the "Between the Flags" program in response to the death of a young patient as a system wide approach for early detection and management of the deteriorating patient in all 242 NSW hospitals. The impact of BTF implementation on the 35 larger hospitals with ICUs has not been reported previously. AIM This study assessed the impact of "Between the Flags" (BTF), a two-tier rapid response system across 35 hospitals with an ICU in NSW on the incidence of in hospital cardiac arrests and the incidence and outcome of patients admitted to an Intensive Care Unit following cardiac arrest and rapid response team activation. METHODS Prospective observational study of BTF registry (August 2010 to June 2016), and the Australian and New Zealand Intensive Care Society Adult Patient Database (January 2008 to December 2016) in 35 New South Wales public hospitals with ICU. Primary outcome studied was the proportion of in hospital cardiac arrests. Secondary outcomes included changes in the severity of illness and outcomes of cardiac arrest admissions to ICU and changes in the volume of rapid response calls. RESULTS The cardiac arrest rate per 1000 hospital admissions declined from 0.91 in the implementation period to 0.70. Propensity score analysis showed significant declines in ICU and hospital mortality, and length of stay for cardiac arrest patients admitted to ICU (all p less then ?0.001). CONCLUSIONS The BTF program was associated with a significant reduction in cardiac arrests in hospitals and ICU admissions secondary to cardiac arrests in 35 NSW hospitals with an ICU. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Thermal proteome profiling (TPP) is based on the principle that, when subjected to heat, proteins denature and become insoluble. Proteins can change their thermal stability upon interactions with small molecules (such as drugs or metabolites), nucleic acids or other proteins, or upon post-translational modifications. TPP uses multiplexed quantitative mass spectrometry-based proteomics to monitor the melting profile of thousands of expressed proteins. Importantly, this approach can be performed in&nbsp;vitro, in&nbsp;situ, or in&nbsp;vivo. It has been successfully applied to identify targets and off-targets of drugs, or to study protein-metabolite and protein-protein interactions. Therefore, TPP provides a unique insight into protein state and interactions in their native context and at a proteome-wide level, allowing to study basic biological processes and their underlying mechanisms. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.Three atomic resolution crystal structures of Photosystem II, in the double flashed, nominal S3 intermediate state of its Mn4 Ca Water Oxidising Complex (WOC), have now been presented, at 2.25, 2.35 and 2.08?Å resolution. Although very similar overall, the S3 structures differ within the WOC catalytic site. The 2.25?Å structure contains only one oxy species (O5) in the WOC cavity, weakly associated with Mn centres, similar to that in the earlier 1.95?Å S1 structure. The 2.35?Å structure shows two such species (O5, O6), with the Mn centres and O5 positioned as in the 2.25?Å structure and O5-O6 separation of ?1.5?Å. In the latest S3 variant, two oxy species are also seen (O5, Ox), with the Ox group appearing only in S3 , closely ligating one Mn, with O5-Ox separation less then 2.1?Å. The O5 and O6/Ox groups were proposed to be substrate water derived species. Recently, Petrie et?al. (Chem. Phys. Chem., 2017) presented large scale Quantum Chemical modelling of the 2.25?Å structure, quantitatively explaining all significant features within the WOC region.